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Record W3183832023 · doi:10.14288/1.0400042

Investigating the in vitro and in vivo anti-resorptive effects of herbal-and TCM-based extracts on Cathepsin K activity

2021· article· en· W3183832023 on OpenAlexaff
Ru Zhou

Bibliographic record

VenuecIRcle (University of British Columbia) · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCalpain Protease Function and Regulation
Canadian institutionsUniversity of British Columbia
Fundersnot available
KeywordsIn vivoIn vitroPharmacologyTraditional medicineMedicineChemistryBiologyBiochemistryBiotechnology

Abstract

fetched live from OpenAlex

Osteoporosis is a chronic skeletal disease primarily affecting post-menopausal women and men over the age of 50. Current pharmacological interventions, such as bisphosphonates (BP) and denosumab, target the bone resorption process and have limitations in efficacy due to the disruption of important bone remodeling mechanisms and thus reducing bone formation and quality. Cathepsin K (CatK) is the major enzyme that is responsible for the breakdown of type I collagen in the bone matrix, therefore inhibitors of CatK have been a new approach to the treatment of osteoporosis without decreasing bone formation. Several active site CatK inhibitors such as odanacatib (ODN) have shown high efficacy in clinical trials, but were not approved due to risks of adverse effects. Adverse effects were postulated to be due to inhibition of CatK normal physiological as well as pathophysiological functions such as its part in the catabolism of essential growth hormones. Exosite inhibitors extracted from red sage plants, such as tanshinone IIA sulfonic sodium (T06) and dihydrotanshinone-1 (DHT-1) have so far shown a potent anti-resorptive effect while demonstrating an increased specificity in targeting the disease-related collagenase activity of CatK. These inhibitors are able to bind at a site on CatK to prevent collagenase activity while leaving other enzymatic activities unaltered. The major aim of my thesis will be to elucidate the in vitro and in vivo efficacy of herbal-based CatK inhibitors in the treatment of osteoporosis. The in vitro and in vivo efficacy of a pan-tanshinone-containing extracts of Salvia Milthorizoa (SM) , and a formulation used in Traditional Chinese medicine where SM is part of a multi-herbal combination (XLGB Pills), which will be compared against a standard-of-care bisphosphonate through the analysis of bone microstructural as well as CatK activity subsequent to these treatments.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.925
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.005
GPT teacher head0.178
Teacher spread0.172 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2021
Admission routes1
Has abstractyes

Explore more

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